Cardiac ultrasonography continues to be used frequently in experimental medicine for certifying in vivo the physiologic and anatomic characteristics of the cardiovascular system. Advances in ultrasound technologies now provide, both for embryos and small animal models of human disease, visualization and contrast enhancement of the in situ beating heart, and useful characterization of its normal and abnormal function. Moreover, these same technologies now allow image-guided, local injection of gene products, biomarkers, and novel therapeutic agents as part of pre- clinical studies of human diseases and their treatment. This Shared Instrumentation Grant proposal, submitted by eleven University of California, San Diego (UCSD) faculty members in the Departments of Medicine, Bioengineering and Pharmacology, requests support to upgrade a first-generation VisualSonics, Inc., instrument (Vevo 770"), dependent upon the older technology of mechanical sector scanning, to a significantly improved model (Vevo 2100") that is dependent upon electronic linear array technology. This newly released system is capable of color Doppler imaging, higher temporal and spatial resolution, improved data management, and a faster and efficient throughput of core laboratory studies. Projects to be pursued with this new instrument, all of which now enjoy NIH support, encompass a relatively broad range of research fields: 1) embryonic development and postnatal cardiac progenitor cells;2) molecular and cellular signaling that controls the performance and cell-cell interactions of the myocardium, 3) angiogenic control factors in exercise performance, 4) genetic mutations that underlie congenital heart disease, and 5) stem cell bioengineering. These investigations are ongoing, in close proximity, on the UCSD campus and depend heavily upon ultrasonography for pursuit of their specific aims. Two other cardiac ultrasound systems, based upon phased array technology, are presently available to basic scientists in cardiovascular medicine at UCSD, but are relatively old and technologically obsolescent. They include: 1) a 10-year old Philips Sonos 5500" system, used at the Seaweed Canyon Physiology Laboratory since 1999, 2) a relatively inexpensive and reconditioned Philips Sonos 5500", purchased by the Department of Pharmacology in 2008. PUBLIC HEALTH RELEVANCE: The proposed instrument upgrade (VisualSonics 2100(tm)) has been designed specifically to study the in vivo anatomy and function of the heart and vascular tree in small animal models of human disease. The instrument can also be used for studies of developmental biology and to test the effects of new therapeutic approaches on cardiovascular dysfunction. This innovative work will incorporate the fields of embryology, molecular cardiology, stem cell biology, regenerative medicine, and bioengineering;it is believed that these research efforts will yield new information on the causes and pathogenesis of diseases and help conceive new diagnostic and therapeutic approaches for many clinical conditions of man.